The Islet Cell Biology Core supports the overall mission of the Penn DRC to prevent, treat, and cure diabetes. Reduced islet beta-cell numbers and function underlie the progression of the full spectrum of diabetes. It is therefore essential for all laboratories investigating causes and potential cures for diabetes to be able to study islet function in relation to their specific models and molecules of interest. The objective of the Islet Cell Biology Core is to provide DRC members with state of the art support including experiment design, islet isolation, and performance of and/or training in an expansive range of assays for physiological and morphological assessment of pancreatic islet function and growth. The Core offers a range of services that generally begins with Islet isolation from rodent models and may be followed by a period of culture by the core. Islet hormone secretion can be assessed in static "batch" incubations or by more informative perifusions that require larger numbers of islets and expensive immunoassays. Depending on the needs and capacity of the investigator laboratory, the core may provide these services in an ongoing manner or it may provide critical training to allow the investigator laboratory to perform the experiments independently over time. The core also has the advanced technology and expertise to perform islet and cell fluorescence imaging (Ca{i}[2+]), perifusion with respirometry, and "closed" respirometry experiments for our investigators. A major advance of the previous grant cycle was an enhanced focus on human islet physiology, capitalizing on the unique strengths of the Penn DRC environment in the area of human islet procurement. By providing unique services and expertise, and continually developing state-of-the art analysis of islet structure and function, the Islet Cell Biology Core remains a critical and valuable component of the Penn DRC.